Lecture 11- haemopoetic dev Flashcards

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1
Q

what is haemotopoesis

A

the biol process which all blood cells are generated

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2
Q

what are the three mature blood cell types in verts

A

erythrocytes (rbc)
myeloids (innate immune syst)
lymphocytes (adaptive immune syst)

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3
Q

what is the function of erythrocytes and number produced daily

A

transport oxygen
2 million
system works non-stop to prouce cells (most common cell in body)

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4
Q

what is a subset of the myeloid

A

granulocytes

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5
Q

what are eg of myeloid

which one not granulocyte

A

neutrophil
eosinophil
basophil
macrophage (*)

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6
Q

what different about macrophages compared to rest of myeloid

A

life span days to years

in others only few days

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7
Q

what are some eg of lymphocytes

A
T cells (inc cytotoxi/helper/regulatory/memory)
B cells (plasma/memory)
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8
Q

what the difference between b and t cells

A

b are less specific

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9
Q

what are megakaryocytes

A

another blood cell
fragments of which are platelets
each produces (2000-5000 platelets)

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10
Q

what is the stem cell all blood cell arise from

A

long term haemopoetic stem cell (LT HSC)

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11
Q

where ar LT hSC found

A

in bone marrow

the micro env conditions very complex and specific - not yet recreate in vivo

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12
Q

when are HSC created

A

in embryonic life

no de novo gen after birth

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13
Q

how does the emergence of the haemopoeitc system in the mouse embryo occur

A

in waves

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14
Q

where are the first blood cells in embryoinic life generated

A

yolk sac

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15
Q

when are the first blood cells generated in the embryo and what blood cells are they

A

9.5

b and t cell

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16
Q

what is the first wave of haemopoesis

A

at E7.25
primitive erythrocytes
macrophages
megakaryocytes

17
Q

where in the yolk sac do first blood cells develop

A

blood island (formed from the migration of cells from primitive streak to yolk sac)

18
Q

what are properties of primitive erythrocytes

A
gone at time of birth
expr embryonic globins 
larger than definitive erythrocytes
efficient distribution of oxygen 
at 8.5 in blood island only
at 9.5 distributed everywhere
19
Q

what is involved in the second wave of haemopoesis

A

in yolk sac at E8.25 () = generation of erythro-myeloid progenitors
in embryo at E9.5 = generation of t and b cell/lymphocytes progenitors

20
Q

where are the erythro-myeloid progenitors generated and where do they migrate for maturation

A
yolk sac (E8.25)
foetal liver (E11.5)
give rise to definitive erythrocytes and all myeloid progenitors
21
Q

what are tissue resident macrophages and where are they derived

A

highly specialised tissue specific macrophages
self renewing
generated during yolk sac haematopoiesis
then migrate to specific tissue and adopt specific fucntions
persist through adult life
maintained by self renewal

22
Q

what is the third wave of haemopoiesis

A

at E10.5

HSC generated in embryo

23
Q

what stages are HSC independent

A

up to E10.5

24
Q

describe evidence that HSC not yolk sac derived

A

as visualised by staining at E8.25 thought were
but grafting experiment with chicks and quail (yolk sac and embryo) showed all cells derived from embryo
hsc only detected within the AGM region at E10.5 (inject from yolk sac - die/ inject from agm only survive)

25
Q

where are hsc foudn in mie through utero

A

E10.5 - AGM
E 11 - foetal liver
E14 foetal spleen
E18 bone marrow

E11.25 yolk sac and placenta

26
Q

what wave of haemopoeisis is called primitive haematopoeisis and what defintive

A

first wave - primitive

others - definitive

27
Q

what is hemangioblast

A

a mesoderm precursor

gives ruse ti blood, endotheium and smooth muscle

28
Q

how does hemangioblast generate blood cells

A

through a hemogenic endothelium intermiediate

29
Q

what is ETV2 and where expr

A

a tf

expr in yolk sac mesoderm at the onset of gastrulation at E7.25

30
Q

what is the role of ETV2 and how determined

A

master regulator of endothelial and blood prgrammes
mesoderm to hemangioblast trasnition
ko - no blood cells or vessels

31
Q

what is SCL

A

a bHLH tf

32
Q

phenotpye of SCL

A

identified at breakpoints in leukaemia
embryo deficiency - lethal
ko - no blood cells but have vessels

33
Q

role of scl

A

required for generation of all blood cell types

hemangioblast to hemogenic endothelium

34
Q

what us runx1

A

a core binding TF

35
Q

phenotypes associated with RUNX1

A

most common gene translocated in leukaemia
deficient - lethal
deficient have primitive erythrocytes but no other cell types
have haemogenic endothelium but no blood cells

36
Q

what is the role of RUNX1

A

endothelial to haematopoetic transition