Stem Cells Flashcards

1
Q

4 characteristics of stem cells

A
  1. remain in undifferentiated state
  2. can make another stem cell and also a new cell that is committed to differentiation when they divide
  3. they can undergo an unlimited number of cell divisions
  4. have potency
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2
Q

what is a totipotent stem cell

A

ability to produce all of the differentiated cells in an organism, including embryonic tissues (placenta)

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3
Q

what is a pluripotent stem cell

A

cell that can give rise to any fetal or adult cell type except extra-embryonic tissues (no placenta)

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4
Q

what is a multipotent stem cell

A

cell that can giverise to multiple lineages

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5
Q

what is a unipotent stem cell

A

can only give rise to one type of undifferentiated cell

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6
Q

what is the concept of asymmetric stem cell division

A

each newly formed daughter cell has a different fate, stem cell plus a future differentiation cell

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7
Q

what is environmental asymmetry

A

daughter cells produced by division of stem cell are initially the same, but environmental influences direct one daughter cell to differentiate

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8
Q

what is divisional asymmetry

A

internal factors direct one of the daughter cells to follow a path of differentiation

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9
Q

1st step in differentiation

A

transit amplifying cell is developed, which divides frequently but for a limited amount of divisions, resulting in the amplification of resulting differentiated cell population

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10
Q

what are transit amplifying cells

A

the first step after a cell has decided that it will differentiate, divides frequently, amplification of resulting differentiated cells

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11
Q

significance of progeny of transit amplifying cells

A

can differentiate in response to environmental cues (extracellular signaling)

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12
Q

what is the impact of extracellular matrix on differentiation

A

physical properties of ECM can determine what type of cell that bone marrow stromal cells can differentiate to

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13
Q

what are bone marrow stromal cells

A

cell found in bone marrow that can differentiate into fat cells, cartilage, or bone cells

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14
Q

what do bone marrow stromal cells develop to on stiff matrix and how?

A

bone cell
because there is a strong adhesion between the cell and the ECM, causes transcription factors YAP and TAZ to become active

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15
Q

what do bone marrow stromal cells develop to on soft matrix and how?

A

fat cell

because there is weak adhesion between cell and ECM, YAP and TAZ remain off

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16
Q

what 5 genes are highly expressed in pluripotent stem cells?

A
  1. Klf4
  2. Lin28
  3. Oct4
  4. Nanog
  5. Sox2
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17
Q

what are the molecular markers of cell differentiation

A

each stage of differentiation is characterized by a different pattern of gene expression

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18
Q

where are somatic stem cells found in adults?

A

niches

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19
Q

what tissues have stem cell niches

A

SHENG

  1. skeletal muscle
  2. hematopoeitic tissue
  3. epidermis
  4. neural tissue
  5. gut epithelium
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20
Q

what type of stem cells are the stem cells in the niche tissue?

A

multipotent

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21
Q

where are stem cells found in the epidermis/glabrous skin?

A

near tips of dermal papillae in epidermis, in the bulge region of hair follicles

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22
Q

what can skin stem cells differentiate into?

A

keratinocytes, sebaceous gland cells, hair cells

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23
Q

how are stem cells distinguished from other cell types in the skin?

A
  1. the stem cells express high levels of beta1 integrin
  2. differentiating cells express keratin-10
  3. transit amplifying cells marked by BrdU incorporation
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24
Q

what do differentiating skin cells express?

A

keratin-10

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25
Q

what do skin stem cells express that distinguish them from other cells

A

beta1 integrin

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26
Q

what do skin transit amplifying cells express

A

marked with BrdU incorporation

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27
Q

where are gut epithelium stem cell niches found

A

crypts in the bottom of pockets along the intestinal wall

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28
Q

what can gut epithelium stem cells differentiate into?

A

absorptive cells (enterocytes), goblet cells, enteroendocrine cells, paneth cells

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29
Q

what occurs once the gut stem cells are differentiated?

A

the cells slide along epithelium upward to cover villus

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30
Q

what type of signaling is utilized in the gut epithelium to control stem cell differentiation?

A

wnt signaling leads to the expression of notch and delta.

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31
Q

explain the use of notch and delta in the gut epithelia

A

paneth cells in the crypt express delta, which activates notch signaling in the stem cells, preventing them from differentiating (lateral inhibition)

32
Q

what are paneth cells?

A

nondividing terminally differentiated secretory cells

33
Q

what role does notch play in the transit amplifying cells in the gut epithelia?

A

notch signaling maintains proliferative state in transit amplifying cells which ultimately give rise to the absorptive cells of the villi

34
Q

what role does delta play during differentiation?

A

expression causes some cells to differentiate into secretory cells

35
Q

where are neural stem cell niches found

A

subventricular zone of lateral ventricle, hippocampus

36
Q

what do neural stem cells differentiate into

A

neurons, glial cells (astrocytes, oligodendrocytes)

37
Q

in humans what is the purpose of neural stem cells in the hippocampus?

A

providing new neurons needed for constant turnover of cells in this region

38
Q

in mice, purpose of neural stem cells in the ventricles?

A

these stem cells constantly produce progenitor cells, that migrate to the olfactory bulb, where they differentiate into neurons to replace the ones constantly lost

39
Q

what are the skeletal muscle stem cells

A

satellite cells (myosatellite cells)

40
Q

where are satellite cells found

A

between sarcolemma of skeletal muscle fibers and the surrounding basal lamina

41
Q

what do the satellite cells do in the muscles

A

lay in quiescent state until muscle damage induces them to re-enter the cell cycle and produce progenitor cells

42
Q

what happens when satellinte cells are activated

A

express high levels of myoD that results in differentiation into myoblasts and ultimately formation of new myofibers

43
Q

where are hematopoietic stem cells found

A

bone marrow

44
Q

what are HSC

A

hematopoietic stem cells capable of indefinite self renewal and gives rise to multipotent progeniors

45
Q

what are MPP

A

multipotent progenitors that are differentiated from HSC

46
Q

what is the CMP

A

common myeloid precursor, derived from the multipotent hematopoietic progenitor, gives rise to GMP and MEP

47
Q

what is GMP

A

granulocyte/macrophage progenitor

48
Q

what is MEP

A

megakaryocyte/erythrocyte progenitor

49
Q

what is a “-blast”

A

cell that has the ability to divide and proliferate, and is the precursor to a fully differentiated cell
A TRANSIT AMPLIFYING CELL!!!

50
Q

what is the CLP

A

common lymphoid progenitor, derived from the multipotent hematopoietic progenitor, gives rise to pro B cells and NK/T cells

51
Q

what do proB cells give rise to

A

pre-B cells which give rise to B cells

52
Q

what do NK/T cells give rise to

A

T cells and NK cells

53
Q

how are hematopoietic cells identified?

A

presence of specific proteins found on the outer surface of their plasma membranes

54
Q

what do HSC’s express?

A

KIT, SCA1 and low levels of CD34 and FLK2

55
Q

how do the stem cell niches maintain their niches?

A

communication between stem cells and supporting cells within their niches

56
Q

example of niche maintenance

A

hematopoietic stem cells must remain in contact with stromal cells within bone marrow to retain stem-ness

57
Q

HSC niche maintenance process

A
  1. stem cells express KIT receptors on their cell surface, which binds to Kit ligand expressed on surface of stromal cells
  2. kit receptor/ligand binding initiates signaling cascade within stem cell that allows the cell to remain stem cell
  3. when stem cell divides, interaction of stromal cells is lost in one of the cells, therefore Kit receptor is no longer active and the cell is committed to differentiation
58
Q

what occurs when an HSC divides in terms of maintenance

A

interaction of stromal cells is lost in one of the cells, and kit receptor is no longer active. the cell is committed to differentiation

59
Q

what tissues are devoid of stem cells

A

auditory epithelium, retinal epithelium

60
Q

is terminal differentiation really terminal?

A

no, in certain conditions terminally differentiated cell can be converted back into pluripotency

61
Q

what is a somatic cell nuclear transfer ? (SCNT)

A

cloning technique where nucleus of terminally differentiated somatic cell is transferred into the cytoplasm of an enucleated egg

62
Q

product of SCNT

A

reproductive and therapeutic cloning (potential for immunological rejection minimized

63
Q

where are embryonic stem cells?

A

derived from inner cell mass of a blastocyst and are pluripotent

64
Q

what is iPS cells

A

induced pluripotent stem cells, terminally differentiated somatic cells (fibroblasts) that are collected from an individual and expressed with oct3/4 and Klf4, which causes the differentiated cell to revert back to a pluripotent, undifferentiated stem cell state, which then can be forced to differentiate into any cell type

65
Q

what is the major difference ethically between SCNT and iPS

A

iPS does not involve the creation and destruction of a human embryo

66
Q

which genes are the master regulators of induced pluripotency

A
  1. Klf4
  2. oct4
  3. Nanog
  4. sox2
67
Q

why are the KONS master regulators?

A

induce their own expression and also induce the expression of each other, generating a self sustaining feedback loop that mainains a stem cell like state

68
Q

1st wave of iPS regrogramming

A

cellular proliferation, metabolism, cytoskeletal organization genes are expressed and genes associated with fibroblast development are repressed

69
Q

2nd wave of iPS reprogramming

A

genes required for embryonic development and stem cell maintenance are induced

70
Q

potential uses for iPS?

A
  1. analyze genetic disease mechanism or for discovery of therapeutic drugs
  2. repair genetic defect by being induced to differentiate in vitro and grafted back into the patient without initiating an immune response
71
Q

what do erythroblasts give rise to

A

erythrocytes

72
Q

what do megakaryoblasts give rise to

A

megakaryocytes, platelets

73
Q

what do monoblasts give rise to

A

monocytes, then macrophages

74
Q

what do myeloblasts give rise to

A

neutrophils

75
Q

what do eosinophiloblasts give rise to

A

eosinophils

76
Q

what do basophiloblasts give rise to

A

basophils