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Topics of Biomedical Science > Gene Structure & Hematology > Flashcards

Gene Structure & Hematology Flashcards

1
Q

What is hematology the study of (2 things)?

A
  1. blood and blood forming organs
  2. normal development, diagnosis, prevention, and treat of blood and bone marrow diseases
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2
Q

Major components of the blood

A

red blood cells, white blood cells, platelets, and plasma

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3
Q

RBCs, WBCs, platelets

A

erythrocytes, leukocytes, thrombocytes

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4
Q

What is blood?

A

a specialized fluid that composes 7-8% of body weight

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5
Q

What percentage of blood is RBC?

A

45

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6
Q

what percentage of blood are plasma and leukocytes?

A

55

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7
Q

What are the functions of blood?

A

transports O2 and nutrients to tissues, fight infection, regulate body temp, prevent blood loss through clotting, bring waste products to kidneys and liver to filter and clean blood

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8
Q

What is hematopoiesis?

A

highly regulated process where hematopoietic stem cells form mature blood cells

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9
Q

Why is hematopoiesis necessary?

A

blood cells have a limited lifespan and precise numbers must be replenished through the renewing of progenitor cells

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10
Q

Homeostasis is important therefore…

A

the regulation of stem cells and progenitor cell proliferation is needed

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11
Q

What are the key characteristics of HSCs?

A

self-renewal and differentiation

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12
Q

Self-renewal

A

process in which stem cells divide and give rise to more stem cells

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13
Q

benefit of self-renewal

A

preserves the stem cell pool

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14
Q

differentiation

A

process in which HSCs develop into mature blood cells with progressive lineage commitment

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15
Q

Categories of HSCs

A

Long term and short term

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16
Q

LT-HSCs

A

primary functions are self-renewal and ability to give rise to all blood lineages/multipotency

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17
Q

ST-HSCs

A

less renewal potential and functions to differentiate into MPP

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18
Q

Human markers on LT-HSC

A

lin-/CD34+/CD38-/CD45RA/CD49f+/CD90+ and lin-/CD34-/CD38-/CD93hi

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19
Q

Human markers on ST-HSC

A

lin-/CD34+/CD38-/CD45RA/CD49f+/CD90+

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20
Q

Mouse markers on LT-HSC

A

CD48-/CD150+/CD34-/low and CD135-/CD201+

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21
Q

Mouse marker on ST-HSC

A

CD48-/low/CD150-/CD135-/CD201-

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22
Q

What can progenitors be classified as?

A

multi-, oligo-, or unipotent

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23
Q

Multipotent progenitors

A

differentiate into multiple cell types and lineages

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24
Q

Oligopotent progenitors

A

different only into a few cell types

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25
Oligopotent progenitor categories
CMPs and CLPs
26
Common myeloid progenitors
futher differentiate into MEG and GMP
27
Common lymphoid progenitor
differentiate into commited precursors that give rise to mature lymphoid cells
28
unitpotent
can only produce one specific blood type
29
Unipotent examples
megakarocyte, erythrocyte, monocyte, granulocyte
30
Where is the first wave?
extraembryonic yolk sac
31
What is in the extraembryonic yolk sac
nucleated RBCs and macrophages are produced
32
Who makes lineage decisions?
small pool of HSCS
33
The small pool of HSCSs choose...
whether to produce new HSCs through self-renewal or to differentiate into daughter cells with capacities to differentiate into mature committed blood cells
34
Types of HSC cell division
symmetric or asymmetric
35
What does symmetric division give rise to?
two daughter cells with the same potential
36
What does symmetric division generate?
two stem cells that remain capable of self-renewals (expansion) and two progenitors poised for commitment (differentiation)
37
Why is symmetric division needed?
essential for rapid generation
38
Downside of symmetric division
lead to depletion of HSCs
39
What does asymmetric division give rise to?
two daughter cells with different functions and multilineage capacity
40
What does asymmetric division generate?
one cell committed to maintain the HSC pool through self-renewal capacity and one cell committed to differentiation
41
Why is asymmetric division important?
allows maintenance of HSC numbers which permits balance between self-renewal and differentiation
42
What are the two proposed models to describe fate decisions?
stochastic and deterministic
43
Stochastic model
HSCs commit to a fate due to intrinsic events but extrinsic signals like cytokines are more supportive
44
Deterministic model
HSCs adopt different cell fate due to direct influence of extrinsic signals; more instructive and cytokines actively influence the decision
45
What is involved in regulation of HSC fate?
bone marrow microenvironment, hematopoietic growth factors, signaling pathways, cytokines, TFs, noncoding RNA, epigenetic regulators
46
What do cytokines and growth factors for HSC fate?
erythropoiesis
47
What do granulocyte colony-stimulating factor do for HSC fate?
neutrophil production
48
What does thrombopoetein (TPO) do for HSC fate?
platelet production
49
What controls gene expression?
transcription factors
50
Transcription factors drive...
lineage decisions and differentiation
51
What are TFs?
DNA binding proteins that play a crucial role in gene regulation by controlling the transcription of specific genes
52
During hematopoeisis what do TFs do?
TFs of different classes intricately regulate HSC fate
53
How are TFs categorized in hematopoiesis?
those that can affects HSCS and early progenitors or those that are lineage specific
54
TF mechanisms
they have the ability to interact with each other and form stable protein complexes bound to cis-regulatory elements (CREs)
55
CRE function
act as regulatory switches to control gene expression
56
How are CREs arranged?
divided into promoters and distal elements away from the transcription start site
57
Expression of TFs in hematopoieses are
context dependent
58
SCL/TAL1 TF
Basic helix-looped protein stem cell leukemia acute lymphoblastic leukemia 1
59
SCL/TAL1 function
multifaceted regulator involved in specification and adult HSCs
60
PU.1
an ETS family TF with multiple roles in hematopoiesis
61
PU.1 function
positively regulates genes in the myeloid and B cell lineage and can work through a mutual antagonism with GATA1
62
GATA1
expressed in lineage committed cells such as erythrocytes, megakaryocytes, and eosinophils
63
GATA2
expressed in HSCs and immature progenitor cells
64
During erythropoeisis, GATA1
regulates multiple erythoid genes
65
What do transcription factors (TF) form to control hematopoietic stem cell (HSC) function?
Distinct networks
66
How do TF interact within the HSC compartment?
They play synergistic and antagonistic roles
67
What have high-throughput studies revealed about TF connections?
They are connected through autoregulation, feedback, and autoactivation
68
What happens to HSC TF networks during differentiation?
They disappear, and TF networks involved in terminal differentiation emerge
69
Why is understanding TF networks important for therapeutics?
Because they are highly regulated and represent a promising area to improve treatments
70
How do noncoding RNAs compare between HSCs and HSPCs?
They are enriched in HSCs compared to HSPCs
71
What is the function of microRNAs (miRNAs) in gene expression?
They repress gene expression by silencing and degrading mRNA
72
Why are miRNAs important for HSCs?
HSCs depend on miRNAs for survival, and over 100 are specifically expressed during hematopoiesis
73
What is the primary function of miRNAs in hematopoiesis?
They regulate transcription factors (TFs) and cytokines during lineage commitment

Topics of Biomedical Science (2 decks)

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