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Stem cells extra > Lecture 2 Overview of embryonic development/niche > Flashcards

Lecture 2 Overview of embryonic development/niche Flashcards

1
Q

What is seen in development in terms of potency?

Where is this seen?

What does this give rise to?

A

Gradual restriction of multipotent cells into committed fates

In the 3 germ layers

Multiple cell types/tissues/orgasn

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2
Q

Initially cells are…

A

Totipotent i.e. give rise to any cell

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3
Q

Totipotent cells become…

A

Pluripotent i.e. able to form all the tissues of the body except the placenta

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4
Q

Pluripotent cells become…

A

Multipotent i.e. able to give rise to many cell types

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5
Q

What happens in the first 3 weeks post fertilisation

A

Body axes are gradually established

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6
Q

What happens in week 3-8 post fertilisation

A

Main organogenesis occurs

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7
Q

What cells are set aside in an undifferentiated state and why?

A

Adult or somatic cells

For building, restoring or regenerating the body of an individual over its lifetime

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8
Q

What other specialised cell is set aside, in an undifferentiated state for the next generation?

A

Gonadal germ cells

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9
Q

What do the germ cells of the gonads give rise to

A

Sperm and egg which fuse to form a zygote

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10
Q

Why are the gonadal germ cells protected?

A

To remain totipotent. This is a biological mechanism to maintain the species as we have a finite life span

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11
Q

When are the gonadal germ cells set aside?

A

As soon as the zygote is made to prepare for the next generation

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12
Q

A ‘tissue specific stem cell’ is ….yet a ‘gonadal germ stem cell’ is….

A

Gradually depleted over Essential for the next generation

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13
Q

In all plants and some animals somatic cells…

A

Can readily form new organisms

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14
Q

In many animals there is an early division between __________ and ________ cells

A

somatic cells

germ cells

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15
Q

What is interesting RE somatic cells in plants

A

Can readily form new organisms

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16
Q

Where are the primordial germ cells determined

A

In a specific location on the edge or outside of the developing embryo

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17
Q

PGCS

A

Primordial germ cells

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18
Q

Where do PGCs migrate to

What do they become here

A

Migrate to the gonad

Become the progenitor population for eggs and sperm

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19
Q

What do you need (2) for the determination of the germ cells

A

Totipotent (plastic) cells

Cell which is capable of undergoing meiosis to reduce 2n diploid status to the n haploid status

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20
Q

Describe how the nematode worm gave us conceptual understanding about the formation of germ cells

A

Nematode worm has a specific number of cells from the one cell stage (lineage can be traced)

Early asymmetric divisions leads to the formation of the P lineage

This cell makes its way to the posterior of the cell

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21
Q

Describe how asymmetric cell division takes place

A

Coupling the polarisation of the cytoplasmic determinants to the oriented plane of cell division

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22
Q

What does the P cells act as

A

Pre germ cell

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23
Q

Throughout asymm divisions what to the P cells inherit

Describe their composition

A

P-granules

Mix of protein and RNAs

24
Q

Where are P-granules located

A

In the cytoplasm, but these are able to get into the nucleus

25
Q

Describe how the P-granules work

A
  1. Binds to DNA of P cell and block almost all transcription thus all differentiation
  2. And in cytoplasm and also block translation (i.e. a fail-safe device)
  3. Promote stem cell fate and cause cells to undergo meiosis (rather than mitosis)
26
Q

Describe what is seen when Nem worm P cells are stained for transcriptional activity

A

No transcriptional activity in the P cell

27
Q

Similar P-cell exist in vertebrates

Where are they found

A

Always posterior

28
Q

What does the developing Xenopus express in the germ cells, just outside of the posterior part of the embryo

A

Nanos = transcriptional blocker

29
Q

In all vertebrates at the very earliest stages of development, a germ cell is established which shows…

A

Little transcription or translation
So no differentiation
Cell have a plastic or pluripotent identity that can undergo meisosis

30
Q

What mechanisms are involved in the shutting down of PGCs

A 
Epigenetic silencing mechanisms i.e.
Histone modifications (methylation and deacetylation) 
DNA methylation
31
Q

Describe DNA methylation

A

Represses gene activity

32
Q

Describe histone modifications

A

Histone proteins govern accessibility of gene promotors - modification of the lysine rich N terminal tails of core histones allows altering of the activity of the DNA which is wrapped around them

33
Q

PGCS arised from __________________

A

Extra-embryonic mesodendodermal cells

34
Q

Where do PGCS stay during axes formation

What is the reasoning behind this

A

Beyond the posterior part of the embryo

Protected form signals which are specifying the body axes of orchestrating cell/tissue/organ differentiation

35
Q

Why are PGCs pluripotent

A

Because genes that code for differentiation factors are repressed transcriptionally and translationally

36
Q

Are PGCs capable of mitotic or meiotic divisions

A

Meiotic

37
Q

When do PGCs migrate

A

Once rapid differentiation of early embryogenesis begins to decrease

38
Q

In drosophila, how are the pole cells visualised?

A

Through probes for Vasa

39
Q

Describe the migration of the germ cells

A

Germ cells passively ride the endoderm and then attach to endoderm and migrate through the midgut to inside the embryo. The germ cells then attach to the mesoderm.

40
Q

What drives the PGCs and gonad precursor cells together to a specific destination?

A

A combination of chemoattractive and repulse cues

41
Q

Where is the final destination of the PGCs

A

Gonadal niche

42
Q

What stage do the PGCs divide through and differentiate at?

A

Divide through larval stage

Differentiate through metamorphosis

43
Q

In ovaries, cells attach to…

A

Stromal caps

44
Q

In testes, cells attach to…

A

Hub cells

45
Q

Describe the migration of the PGCs in chick/mouse/human

A

Primordial germ cells stay out of the embryo (in the extraembryonic territory), while the major inductive events occur that orchestrate body axes formation and early organogenesis. Then PGCs migrate through the posterior gut (hindgut) along a fibronectin train then leave the gut to move more laterally to the genital ridges. Where they are ultimately found in protective niche – the gonads

46
Q

What is the function of the genital ridges/gonads?

A

The genital ridges/gonads provide a specialist microenvironment that protects the PGCs in their pluripotent state. This supports their meiotic divisions and the formation of eggs or sperms.

47
Q

Describe what recent literature has found on how rudimentary eggs and sperm can be made from stem cells

A
  • Fibroblast skin cells were dedifferentiated and reprogrammed back to an embryonic-like state i.e. pluripotent state through iPS-cell technology
  • Cells were then redirected to a specific fate e.g. a PGC identity
  • The PGC are then placed in mouse testes or ovaries to get the differentiation of eggs or sperm
  • Both sperm and egg could be used for in vitro fertilisation
  • Could provide a cure for infertility
  • Not done in humans – what are the ethical implications of this
48
Q

Describe the travelling stem cell niche idea

A

Support cells travel with PGCs secreting SCF to maintain the undifferentiated cell phenotype

49
Q

What is SCF

A

Stem cell factor

50
Q

What is the affect of a mutation which means SCF is unable to be produced

A

Stem cells are no longer protected and would differnetiate

51
Q

What is the affect of a mutation which means that the chemoattractant is no longer produced

A

Would get stuck in the gut and would fail to make it to the niche

52
Q

Describe how PGCS can lead to formation of teratomas

A

Failure to migrate to the protective niche would lead to the formation of teratomas

53
Q

Where are the teratomas located?

A

At the mouth or posterior hind gut

54
Q

What does the teratoma contain?

A

All the cells/tissues of the body

55
Q

What do the teratomas show about the potency of PGCs

A

That they are totipotent

56
Q

What do teratomas show about normal development?

A

That it is not just about altering fate, but about altering fate in a way that is coupled to axis formation and proper morphogenesis

Stem cells extra (3 decks)

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